Previously, three tissue specific antigens termed S, P, and U located in the outer retina were implicated in the pathogenesis of various forms of experimental autoimmune uveitis. The first two have been isolated, identified, and the histopathologic manifestations characterized. Little is known about the third antigen, U-antigen, which is located at the choroidal base of the retinal pigment epithelium, nor the range of ocular histopathology it might produce. A specific aim is to isolate and characterize this antigen immunochemically, and define the nature of lesions produced. Fractionation of this antigen will be undertaken using a combination of sucrose density gradient ultracentrifugation and chromatographic steps. The antigen will be analyzed immunologically and by electrophoretic techniques, following which the histopathologic manifestations will be characterized in guinea pigs injected with graded doses of the antigens. This work is expected to define a third model of autoimmune uveitis with a potential relationship to clinical situations in man. Additional aims are to define the immunologic mechanism of retinal S-antigen induced autoimmune uveitis by adoptive transfer of antigen stimulated lymphocytes in strain 13 guinea pigs. These approaches are consistent with our longer term objectives of defining the role of specific autoantigens and immunologic mechanisms of experimental and clinical uveitis.